This project will examine the role of energy failure in brain damage from status epilepticus both in neonates and in adults. Our preliminary results disprove the generally accepted idea that status epilepticus does not produce profound energy failure in the absence of systemic complications such as anoxemia. In addition, recent results from other laboratories suggest that the classical bicuculline model of status epilepticus is not adequate to study the mechanisms of cell death. This project will use reliable models of status epilepticus which routinely produce neuronal necrosis in vulnerable brain regions. These models will use the convulsants bicuculline in the newborn marmoset monkey; flurothyl in adult rats; and electrical stimulation of the perforant path in rats. Preliminary results suggest that in these models neuronal necrosis will be sufficiently predictable and widespread so that parallel biochemical studies on the mechanism of cell injury can be conducted. In those biochemical studies, ATP, phosphocreatine, glucose, glycogen and lactate will be measured in micropunch biopsies taken from key regions of brains fixed with either liquid nitrogen or microwave irradiation during status epilepticus. We predict that energy failure will invariably be observed in areas where selective neuronal necrosis develops, and that lactate accumulation will be seen in areas in hypermetabolic infarction.